Nanoparticles are small object in a nano scale size, that behaves as a whole unit in terms of its transport and properties. Nanoparticles may exhibit size-related properties that differ significantly from those observed in fine particles or bulk materials. Methods for the preparation of gold nanoparticles have previously been reported (for example, J. Turkevich, et al., Discuss. Faraday. Soc. 1951, 11, 55-75; J. Kimling, et al, J. Phys. Chem. B 2006, 110, 15700-15707; G. Frens, Colloid & Polymer Science 1972, 250, 736-741; G. Frens, Nature (London), Phys. Sci. 1973, 241, 20-22; M. Brust et al., J. Chem. Soc., Chem. Commun. 1994, 7, 801-802; Manna, et al. (2003) Chem. Mater. 15 (1):20-28; S. D. Perrault; W. C. W. Chan (2009) J. Am. Chem. Soc. 131 (47): 17042; M. N. Martin et al., Langmuir 26 (10): 7410). Colloidal gold is often prepared by reduction of gold halides monodispersed particles with a diameter of 10±60 nm were described by Frens using sodium citrate for the reduction of HAuCl4.
Gold hydrosol is a typical lyophobic colloid, the particles of which bears a large negative surface charge (the surface potential is ˜50 mV) and, hence, it is stable only in very low-ionic-strength solutions. In lyophobic systems, the dispersion medium and the dispersed phase are substantially different in the chemical composition and the interface structure, as a result of which the surface forces at the interface are uncompensated. Therefore, these systems are thermodynamically unstable and require special stabilization.
Stabilizing gold nanoparticles: a strong negative charge of the gold particle surface provides their strong adsorption interactions with high-molecular-mass compounds. Sulfur and gold atoms are known to form dative bonds. Alkane thiol linkers HS(CH2)nR(R═COOH, OH or SO3H; n=11±22) are being used to achieve stronger attachment of bio-molecules to gold particles. Interactions of these linkers with gold afford thiolates which form a monolayer on the particle surface.
In recent years, synthetic polymers, such as polyethylene glycol (PEG), polyethyleneimine, polyvinylpyrrolidone, poly-(vinyl acetate), polyamidoamine (dendrimer), polydithiafulvene, chitosan, and the like, have found application in the synthesis of mono-dispersed colloidal gold (CG). Particles formed in the presence of these polymers are characterized by a higher size and shape uniformity. Unfortunately, the synthesis methods and stabilizers which have been used for producing stable gold nanoparticles did not provide the optimal gold nanoparticles for medical use, which needs highly stable and very concentrated metal nanoparticles in aqueous dispersion. Uses for metal nanoparticles in medical applications have been proposed, such as, for example, in U.S. Pat. No. 6,955,639, which is directed to methods of enhancing radiation effects with metal nanoparticles.
There still remains a need in the art for the preparation of metal nanoparticles that exhibit enhanced properties such as improved stability and solubility, reduced toxicity, enhanced bioavailability, improved pharmacokinetics, for their use in treatment and diagnosis of various health related conditions.